Lung Cancer
Conditions
Keywords
stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer
Brief summary
RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed disodium together with gemcitabine may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different schedules of pemetrexed disodium and gemcitabine to compare how well they work in treating patients with stage IIIB or stage IV non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * Compare response rates in patients with stage IIIB or IV non-small cell lung cancer treated with two different treatment schedules of pemetrexed disodium and gemcitabine hydrochloride. Secondary * Compare time-to-event efficacy variables in patients treated with these regimens. * Compare progression-free and overall survival of patients treated with these regimens. * Determine the overall toxicity of these regimens in these patients. OUTLINE: This is a multicenter, open-label, randomized study. Patients are stratified according to disease stage (IIIB vs IV) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. * Arm II: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 2 years. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
Interventions
DRUGgemcitabine HCL
1250 mg/m\^2 administered through 250 cc NS (normal saline) IV (intravenous) infusion over 30 minutes at days 1 & 8 of each cycle (21 days) x6 cycles.
DRUGpemetrexed disodium
500 mg/m\^2 administered through 100 mL NS IV infusion over 10 minutes at day 1 of each cycle.
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) * Stage IIIB (with controlled pleural effusion) OR stage IV disease * At least 1 measurable lesion whose longest diameter is ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan * No medically significant third-space fluid collection (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures * No documented brain metastases unless all of the following criteria are met: * Successful local therapy has been completed * At least 2 weeks since prior corticosteroids * Brain imaging required for symptomatic patients only (to rule out brain metastases) * Concurrent enrollment in clinical trial MCCRC-RC0527 required PATIENT CHARACTERISTICS: * Life expectancy ≥ 12 weeks * ECOG performance status 0-1 * Absolute neutrophil count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9.0 g/dL * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 3 times ULN * AST and ALT ≤ 3 times ULN (5 times ULN for liver involvement) * Creatinine clearance ≥ 45 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to take folic acid, cyanocobalamin (vitamin B12) supplementation, or dexamethasone and corticosteroids * Able to interrupt intake of aspirin and nonsteroidal anti-inflammatory agents for a total of 5 days * No severe and/or uncontrolled medical conditions, including any of the following: * Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication * Angina pectoris * Congestive heart failure within the past 3 months, unless ejection fraction \> 40% * Myocardial infarction within the past 6 months * Cardiac arrhythmia * Diabetes * Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung * New York Heart Association class III or IV heart disease * Clinically significant infection * No other serious medical condition or illness that would preclude study participation * No peripheral neuropathy ≥ grade 2 * No other malignancy within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the cervix, or low-grade (Gleason score ≤ 6) localized prostate cancer * No significant weight loss (≥ 10%) within the past 6 weeks * No investigator site personnel directly affiliated with the study, or immediate family (i.e., spouse, parent, child, or sibling, whether biological or legally adopted) * No employees of Eli Lilly (i.e., employees, temporary contract workers, or designees responsible for conducting the study) * Immediate family of Eli Lilly employees may participate in Eli Lilly-sponsored clinical trials, but are not permitted to participate at an Eli Lilly facility PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 2 weeks since prior corticosteroids * At least 4 weeks since prior radiation therapy involving \> 25% of the bone marrow and recovered * At least 30 days since prior investigational therapy * No prior radiation therapy to the whole pelvis * No prior systemic chemotherapy for advanced non-small cell lung cancer * No prior pemetrexed disodium and/or gemcitabine hydrochloride * No prior or concurrent sorafenib tosylate and/or temsirolimus * No concurrent Hypericum perforatum (St. John's wort) * No other concurrent antitumor therapy * No concurrent agents that stimulate thrombopoiesis * Concurrent palliative radiation therapy allowed * Concurrent corticosteroids allowed for adrenal insufficiency or severe nausea and vomiting
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Confirmed Responses | Two consecutive evaluations at least 6 weeks apart (up to 2 years) | Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 6 weeks apart. \> \> Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Time from registration to progression or death (up to 2 years) | Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who are alive and progression free being censored on the date of their last evaluation. |
| Overall Survival | Death or last follow-up (up to 2 years) | Overall survival time was defined as the number of months from registration to the date of death or last follow-up |
| Adverse Event | Gemzar x2 Arm every 21 days, Gemzar x1 Arm every 14 days (up to 2 years) | Number of patients that experienced adverse events (grade 4 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0 |
Countries
United States
Participant flow
Recruitment details
19 patients were enrolled from 9 medical clinics between November 3, 2006 and August 10, 2007.
Participants by arm
| Arm | Count |
|---|---|
| Gemzar x2 Treat subjects with 2 dosings/cycle of Gemzar x6 cycles. | 10 |
| Gemzar x1 Treat subjects with 1 dosing/cycle of Gemzar x9 cycles. | 9 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Insurance or Other medical condition | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Gemzar x2 | Gemzar x1 | Total |
|---|---|---|---|
| Age, Continuous | 70.5 Years | 63 Years | 66 Years |
| Lung Stage IIIB w/pleural effusion - N3 or T4 | 2 Participants | 2 Participants | 4 Participants |
| Lung Stage IV - Distant Metastasis | 8 Participants | 7 Participants | 15 Participants |
| Performance Score 0 - Fully Active | 4 Participants | 4 Participants | 8 Participants |
| Performance Score 1 - Ambulatory, restricted strenuous activity | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 10 participants | 9 participants | 19 participants |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 10 | 9 / 9 |
| serious Total, serious adverse events | 4 / 10 | 5 / 9 |
Outcome results
Primary
Number of Patients With Confirmed Responses
Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 6 weeks apart. \> \> Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions.
Time frame: Two consecutive evaluations at least 6 weeks apart (up to 2 years)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemzar x2 | Number of Patients With Confirmed Responses | 2 participants |
| Gemzar x1 | Number of Patients With Confirmed Responses | 0 participants |
Secondary
Adverse Event
Number of patients that experienced adverse events (grade 4 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0
Time frame: Gemzar x2 Arm every 21 days, Gemzar x1 Arm every 14 days (up to 2 years)
Population: All patients that began protocol treatment are included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gemzar x2 | Adverse Event | 6 Participants |
| Gemzar x1 | Adverse Event | 4 Participants |
Secondary
Overall Survival
Overall survival time was defined as the number of months from registration to the date of death or last follow-up
Time frame: Death or last follow-up (up to 2 years)
Population: One patient in Arm B was a major violation and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemzar x2 | Overall Survival | 5.1 months |
| Gemzar x1 | Overall Survival | 8.1 months |
p-value: 0.56Log Rank
Secondary
Progression-free Survival
Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who are alive and progression free being censored on the date of their last evaluation.
Time frame: Time from registration to progression or death (up to 2 years)
Population: One patient in Arm B was deemed a protocol violation and was not include din this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemzar x2 | Progression-free Survival | 1.66 months |
| Gemzar x1 | Progression-free Survival | 5.04 months |
p-value: 0.015Log Rank